Methyl acetate

Endpoint summary

Key value for chemical safety assessment

Toxic effect type:

dose-dependent

Effects on fertility

Description of key information

There are no data on reproductive toxicity of methyl acetate. However, due to the rapid hydrolysis of this compound it is justified to base hazard assessment with respect to reproduction on the toxicological properties of the immediate metabolites acetic acid and methanol. Acetic acid appears to be of less relevance, since there are no indications of a fetotoxic or teratogenic potential in literature. For methanol some embryo-/fetotoxic and teratogenic effects were demonstrated in rodents at relatively high maternal toxic concentrations. A NOEC/fertility for methanol of 1,000 ppm (1,300 mg methanol/m³) was derived from a 2-generation inhalation study in rats (NEDO, 1987). This value can be converted to NOAEC/fertility of about 3,000 mg methyl acetate/m³.

In a sperm-fertility study on mice with methanol a slight, but statistically insignificant increase in sperms abnormalities (1.86 +-0.91% vs. 1.12 +-0.39% in the water control) was observed, while the treatment with cyclophoshamide (100 mg/kg) resulted in an about 5-fold increase (5.84 +-1.94). The LOEC/fertility for methanol in this study on mice is 1,000 mg/kg bw/day (Ward et al., 1984). This value can be converted to a corresponding dose LOAEC/fertility of ca. 2311 mg/kg bw/day for methyl acetate.

Effect on fertility: via oral route

Endpoint conclusion:

no study available

Effect on fertility: via inhalation route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEC

3 000 mg/m³

Study duration:

chronic

Experimental exposure time per week (hours/week):

168

Species:

rat

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

Methyl acetate

Methyl acetate is rapidly hydrolysed after intake. Due to the rapid hydrolysis of the substance no relevant systemic exposure to the parent compound was observed. Accordingly, the toxicological properties of the immediate metabolites are taken into consideration for evaluation of methyl acetate toxicity with respect to reproductive and developmental toxicity. The cleavage products relevant for the assessment are methanol and acetic acid. The same conclusion was drawn in the EU risk assessment on methyl acetate (EU RAR 2008).

Acetic acid

No animal data is available for acetic acid, but regarding the longterm human experience with acetic acid in both the industrial and the food context no relvant effects on fertility have to be expected. More information can be withdrawn from the respective REACh dossier of acetic acid. Acetic acid is the main component of vinegar and a natural constituent of the diet. It occurs endogenously in the body since it is also produced endogenously in animals and plants and is involved in intermediate metabolism via the citric acid cycle. Acetic acid is rapidly metabolised in plasma and most tissues, with a half-life of the order of a few minutes (3-5 min, depending on dose) (Freundt, 1973, as cited by ECHA, 2012). Acetate is readily converted to acetyl-CoA, which enters the citric acid cycle, being converted eventually to carbon dioxide. Only a small amount (~0.6 %) of acetic acid is excreted unchanged, in the urine as acetate (Smith et al., 2007).

EFSA (2008a) concluded in the DAR for acetic acid that "Long term toxicity/carcinogenicity studies in animals with oral exposure are not necessary, considering that humans are exposed to orally ingested acetic acid from various food sources and there is no evidence that such exposure is causally related to toxic effects and an increased cancer incidence."

In the USA Acetic acid is listed on the Generally Recognized As Safe (GRAS) list of food additives (US FDA 2018). The WHO, under the Joint FAO/WHO Expert Committee on Food Additives (JECFA) (WHO, 1998) as well as EFSA (2013) do not consider necessary the establishment of an Acceptable Daily Intake (ADI) and Acute Reference Dose (ARfD) for oral intake of acetic acid by consumers. This is assigned to substances considered to have very low toxicity, in particular, those considered normal constituents of food or metabolites in humans as it is the fact for acetic acid.

On this basis of its low toxicity and its natural occurrence in food and in the body, it is not considered  necessary to establish neither a multigeneration study nor any postnatal evaluation or developmental toxicity studies for acetic acid.

Fertility studies with methanol (NEDO, 1987)

A 2-generation study with Sprague Dawley rats (NEDO, 1987) had been performed in accordance to a former OECD guideline for testing of chemicals of October 1980. Groups of 30 animals/sex/dose group (F0 generation) were exposed to 1,000, 100, and 10 ppm methanol (whole body/continuously) from 8-week-old through either end of mating period (for males at 16-week-old or thereafter) or through the mating and gestation period to the end of lactation (females). F1 generation males were exposed from birth to the end of mating (at 14-week-old or thereafter) and F1 generation females from birth through mating, gestation, lactation to weaning of their pups (21 days after delivery). F2 generation males and females were exposed from birth to 21-day-old, and in addition, one animal/sex/litter further exposed up to 8 week old. In general, litter sizes were reduced to 8 pups 4 days after birth. At 21 days after birth, 2 animals/sex/litter were selected for use as subsequent breeders, respectively for use in various other examinations. Remaining pups were sacrificed and subjected to a necropsy.

Blood levels of methanol for the low-dose (10 ppm) and mid–dose (100 ppm) groups were almost identical with the control group. For the high-dose group (1000 ppm), it was 53 ppm and 99 ppm for males and females, respectively. This finding corresponds to results on the concentration of methanol in blood following after exposure to methyl acetate as being determined in studies on the toxicokinetic behaviour of methyl acetate.

A decrease of body weight gain was found in the high-dose group but was not due to a toxic effect but due to acclimatisation. The decreases in food consumption have the same reason.

The descenus testis, one of the indices to evaluate pupal development after birth, occurred significantly earlier in the high-dose group for the F1 generation (0.5 days) and the F2 generation (1 day). It is supposed that the earlier the fetal development, the earlier the descenus testis occurs. When using the event as a direct index to evaluate fetal development, it was put into correlation with body size. When the mean body weights were arranged by day of descenus testis revelation, it was shown that the event occurred earlier in heavier animals than in lighter ones for each group. This tendency was more obvious for F2 pups (1 day).

As for organ weights of F1 animals, significant decreases in brain weight were observed in high-dose (1000 ppm) males and females at 8 weeks-old necropsy, and similar results were obtained for males at 16-weeks-old necropsy (after mating) and for females at 24-weeks-old necropsy (after delivery and lactation). In F2 animals also, significant decreases in brain, pituitary and thymus weight were observed in high-dose males and females at 8-weeks-old necropsy. Histopathological examination, however, revealed no change suggesting the effect of treatment in any of these organs.

Since such decrease was observed for only the brain weight and no other parameter, on order to confirm its relationship with the treatment and to know what period after birth such changes would appear, an additional sub-study was done in which rats of the same strain were exposed to 0, 500, 1000 and 2000 ppm of methanol gas. Dose-related decrease in brain weight was noted at > 1000 ppm; this appeared as soon as 3 weeks after birth.

The decreases were attributable to the decreases in weight of the cerebrum and cerebellum but not the olfactory bulb.

Although the study by NEDO (1987) could not fully explain the decrease in brain weight, it was clear that exposure to 1000 ppm of methanol gas during gestation and lactation period caused some changes. But, based on the fact that the other examinations, learning ability test included, did not reveal any abnormalities, the toxic effect of methanol was considered to be light.

Sperm-fertility was studied on mice with methanol. The effects in sperms abnormalities were slight, but statistically insignificant. The LOEC/fertility for methanol in this study on mice is 1,000 mg/kg bw/day (Ward et al., 1984).This value can be converted to a corresponding dose LOAEC/fertilityof ca. 2311 mg/kg bw/day for methyl acetate.

Compared to these data from animal experiments, in humans blood methanol concentrations of about 7-8 μg/ml had been determined after external inhalation exposure to 200 ppm methanol (MAK value) for 6 hours (Lee et al., 1992). In addition, from a PBPK model of inhaled methanol in humans (Perkins et al., 1995) it is obvious that methanol blood concentrations after 8-hour exposure to methanol vapours differ for humans and for laboratory animals, e.g. rats and mice. For instance, predictions from this model indicate about 3.5 to 7 fold lower methanol blood concentrations for humans after 8-hour exposure to 1,000 ppm methanol vapours as compared to blood concentrations in mice.

  

Conclusion on effects on fertility

There are no data on fertility effects of methyl acetate. However, due to the rapid hydrolysis of this compound it is justified to base the hazard assessment with respect to effects on the fertility on the toxicological properties of the immediate metabolites methanol and acetic acid. For acetic acid no animal data is available but regarding the longterm human experience with acetic acid in both the industrial and the food context no relvant effects on fertility have to be expected. For methanol animal data is available. In a two-generation-study in rats, which were continuously exposed to 10, 100, and 1,000 ppm methanol, no effects had been observed on parameters of reproductive capacity and capability of the first and the second generation. During F1 and F2 progeny postnatal development, subtle weight changes (brain) had been reported for the 1,000 ppm exposed groups, however, without any relevance for postnatal morphological and/or functional development.

In a sperm-fertility study on mice with methanol a slight, but statistically insignificant increase in sperms abnormalities was observed. The LOEC/fertility for methanol in this study on mice is 1,000 mg/kg bw/day (Ward et al., 1984). This value can be converted to a corresponding dose LOAEC/fertility of ca. 2311 mg/kg bw/day for methyl acetate.

Literature

ECHA (European Chemicals Agency), 2012. Acetic acid, CAS 64-19-7. Available from http://apps.echa.europa. eu/registered/data/dossiers/DISS-9d8c7866-b374-5d28-e044 -00144f67d249/DISS-9d8c7866-b374-5d28-e044 -00144f67d249_DISS-9d8c7866-b374-5d28-e044-00144f67d249.html (accessed 19/02/2012).

EFSA (European Food Safety Authority), 2008a. Draft Assessment Report (DAR): Acetic Acid. Vol. 3, Annex B, part 2, B.6 (Aug, 2008).

EFSA (European Food Safety Authority) (2013). Conclusion on the peer review of the pesticide risk assessment of the active substance acetic acid. EFSA Journal. 11(1):3060.

EU RAR, 2008: European Risk Assessment Report - Methylacetate. European Chemicals Bureau, Institute for Health and Consumer Protection, 1st Priority Liste; Volume 34; EUR 20787 EN.

Freundt KJ, 1973. On the pharmacokinetics of the ethanol metabolite acetate: elimination from the blood and cerebrospinal fluid. Arzneimittelforschung, 23, 949-951. As cited by ECHA, 2012.

Smith GI, Jeukendrup AE and Ball D, 2007. Sodium acetate induces a metabolic alkalosis but not the

increase in fatty acid oxidation observed following bicarbonate ingestion in humans. Journal of

Nutrition, 137, 1750-1756.

NEDO (1987). Toxicological Research of methanol as a fuel for Power Station, Summary Report on Tests with Monkeys, Rats and Mice. New Energy Development Organization. Tokyo, Japan.

Nelson BK, Brightwell WS, MacKenzie DR, Khan A, Burg JR, Weigel WW, Goad PT (1985). Teratological assessment of methanol and ethanol at high inhalation levels in rats. Fundam. App. Toxicol. 5, 727-736.

Lee EW, Terzo TS, D`Arcy JB, Gross KB, Schreck RM (1992). Lack of blood formate accumulation in humans following exposure to methanol vapor at the current permissible exposure limit.of 200 ppm. Am. Ind. Hyg. Assoc. J. 53, 99-104.

Perkins RA, Ward KW, Pollack GM (1995). A Pharmacokinetic model of inhaled methanol in humans and comparison to methanol disposition in mice and rats. Environmental Health Perspectives 103, 726-733.

Rogers JM, Mole ML, Chernoff N, Barbee BD, Turner C, Logson TR, Kavlock RJ (1993). The developmental

toxicity of inhaled methanol in the CD-1 mouse, with quantitative dose-response modeling for estimation of benchmark doses. Teratology 47, 175-188.

US FDA (United States Food and Drug Administration) (2018). Code of Federal Regulations. Title 21: Volume 3. Section § 184.1005 - Acetic acid. Part 184 – Direct Food Substances Affirmed as Generally Recognized As Safe (GRAS). Subpart B - Listing of Specific Substances Affirmed as GRAS. [47 FR 27814, June 25, 1982]. Date: 2018-04-01.

Ward J.B. Jr. et al. (1984): Sperm count, morphology and fluorescent body frequency in autopsy service workers exposed to fromaldehyde. Mutation Research, 130: 417 - 424.

WHO (World Health Organization) (1988). Safety Evaluation of Certain Food Additives and Contaminants. Saturated Aliphatic Acyclic Linear Primary Alcohols, Aldehydes, and Acids. WHO Food additives Series 40. Prepared for the Forty-ninth meeting of the Joint FAO/WHO Expert Committee on Food Additives (JECFA). World Health Organization, Geneva. 1998.

Effects on developmental toxicity

Description of key information

There are no data on developmental toxicicity of methyl acetate. However, due to the rapid hydrolysis of this compound it is justified to base hazard assessment with respect to developmental toxicicity on the toxicological properties of the immediate metabolites. Concerning the metabolites of methyl acetate, acetic acid appears to be of less significance, since there are no indications of a fetotoxic or teratogenic potential, whereas for methanol some embryo-/fetotoxic and teratogenic effects were demonstrated in rodents, however at relatively high concentrations, respectively maternal toxic concentrations only.

A NOAEC/developmental toxicity for methanol of 1,000 ppm (1,300 mg methanol/m³) was derived from two studies in mice (Rogers et al., 1993) and rats (NEDO, 1987) from intermittent as well as from continuous inhalatory exposure, which can be converted to a NOAEC/developmental toxicity of about 3,000 mg methyl acetate/m³.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

257 mg/kg bw/day

Study duration:

subacute

Species:

rat

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEC

3 000 mg/m³

Study duration:

subacute

Species:

rat

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Additional information

Methyl acetate

Methyl acetate is rapidly hydrolysed after intake.

Due to the rapid hydrolysis of the substance no relevant systemic exposure to the parent compound was observed (see Toxicokinetic chapter) Accordingly, the toxicological properties of the immediate metabolites are taken into consideration for evaluation of methyl acetate toxicity with respect to reproductive and developmental toxicity. The cleavage products relevant for the assessment are methanol and acetic acid.  The same conclusion was drawn in the EU risk assessment on methyl acetate (EU RAR 2008).

 

Acetic acid

The available data on acetic acid indicates that acetic acid is not teratogenic in vivo. Teratogenic evaluation of apple cider vinegar was made in rabbits. The administration of up to 1.6 g per kg body weight of the test material daily to pregnant rabbits (days 6 through day 18 of gestation) had no clearly discernible effect on nidation or on maternal or fetal survival. The number of abnormalities seen in either soft or skeletal tissues of the test groups did not differ from the number occurring spontaneously in the sham-treated controls. Sodium acetate displayed no teratogenicity in the developing chicken embryo at levels up to 200 mg per kg of egg when injected into the air cell or yolk of unincubated eggs, or at levels up to 100 mg per kg egg when injected into the air cell or yolk of eggs after 96 hours of incubation (cited from NTIS, 1977).

Supporting Developmental toxicity data on acetic acid as released from methyl acetate can further be gathered from tert-butyl acetate (TBAc). Similar to methyl acetate TBAc is rapidly hydrolyzed to acetic acid (Groth and Freundt, 1994; MAK, 2016). A developmental toxicity study of tert-butyl acetate (TBAc) in rats shows embryotoxicity in form of visceral and skeletal variations at a maternally toxic dose in excess of the limit dose (i.e., 1,600 mg/kg/ day) and is minimally embryotoxic, showing the same variations, at  adose (i.e., 800 mg/kg/day) that did not induce signs of maternal toxity (Yang et al., 2007). However, no evidence for the teratogenicity of TBAc was noted in rats. The NOAEL for maternal toxicity was 800 mg/kg b.w. per day. The NOAEL for developmental toxicity was 400 mg/kg b.w. per day. The MAK commission (MAK, 2016) provided a plausible rationale on the observed embryotoxicity at high doses: " On the basis of the consistent findings with tert-butyl alcohol in developmental toxicity studies (skeletal variations and the absence of teratogenicity), it may be assumed that the foetotoxic effects that were observed in the studies with tert-butyl acetate were induced by the tert-butyl alcohol metabolite or its secondary metabolites."

Based on the available data on tert-butyl acetate and on acetate and tert-butanol, its major metabolites, EFSA (2012) concluded that tert-butyl acetate do not give rise to concerns regarding systemic toxicity, developmental toxicity or genotoxicity. 

It can be concluded that there are no indications that the hydrolysis product acetic acid has a relevant contribution to the developmental toxicity potential of methyl acetate.

 

Methanol

In the developmental toxicity studies, after continuous inhalatory exposure of rats, impaired development of the offspring (reduced numbers of live fetuses, resp. of live pups per litter, increased number of late resorptions, reduced fetal body weight, fetal visceral and skeletal abnormalities, postnatal mortality) was observed at concentrations of 5,000 ppm together with signs of maternal toxicity (reduced body weight gain), whereas at the next lower exposure level (1,000 ppm) such effects were no longer demonstrated. After intermittent inhalatory exposure of rats (7 hours/day) developmental effects (fetal visceral and skeletal abnormalities, reduced fetal body weight) were induced at concentrations of 10,000 ppm, but not at exposure levels of 5,000 ppm Nelson et al., 1985; 1990).

For the inhalatory route of exposure, rats during the gestational period appeared to respond more sensitive to a whole-day continuous exposure test design than to daily intermittent (7 hours/day) inhalation exposure of methanol. According to this, the embryo-/fetotoxic effects as observed at 5,000 ppm in the study of NEDO (1987) were accompanied by clearly impaired maternal conditions. At daily intermittent exposure of rats during gestation, fetal visceral and skeletal abnormalities as well as exencephaly and encephalocelia had been revealed for concentration levels of 10,000 and 20,000 ppm, at which feed intake, water consumption and body weights of their dams had not been significantly affected, thus indicating a substance-specific potential for the induction of structural abnormalities. This is further supported by the findings from mice experiments (Rogers et al., 1993), for which data are only available from intermittent exposure during gestation. As to mice, indications for maternal toxicity in terms of lower maternal weight, clinical signs and occasional maternal deaths were reported for concentration levels of 7,500 ppm and higher. However, as in rats, fetal structural abnormalities were already observed at lower concentration levels of 2,000 and 5,000 ppm.

As to the methanol-induced fetotoxic and teratogenic effects observed in the experiments with rodents, these were reported from external exposures during the gestational period leading to methanol concentrations in blood of the dams of about 500 μg/ml in mice (Rogers et al., 1993) and of about 2,000 μg/ml in rats (Nelson et al., 1985) with intermittent inhalatory exposure. No such effects were seen at external exposures leading to blood methanol concentrations in dams of about 63-130 μg/ml in mice (Rogers et al., 1993) with intermittent inhalatory exposure during the gestational period and of 53 and 99 μg/ml in male and female rat offspring (at 9-weeks-old) with continuous inhalatory exposure (NEDO, 1987) during the pre-and postnatal developmental period.

Compared to these data from animal experiments, in humans blood methanol concentrations of about 7-8 μg/ml had been determined after external inhalation exposure to 200 ppm methanol (MAK value) for 6 hours (Lee et al., 1992). In addition, from a PBPK model of inhaled methanol in humans (Perkins et al., 1995) it is obvious that methanol blood concentrations after 8-hour exposure to methanol vapours differ for humans and for laboratory animals, e.g. rats and mice. For instance, predictions from this model indicate about 3.5 to 7 fold lower methanol blood concentrations for humans after 8-hour exposure to 1,000 ppm methanol vapours as compared to blood concentrations in mice.

In a study from Rogers et al. (1993) with CD-1 mice dams were exposed to 15,000, 10,000, 7,500, 5,000, 2,000, and 1,000 ppm methanol by inhalation from day 6 to 15 of gestation (7 hours/day). There were no visible signs of intoxication of dams following exposure to any level of methanol in this study. One dam died in each of the 7,500, 10,000, and 15,000 ppm methanol exposure groups, but nodose-response relationship was evident for maternal death. No other effects were seen in the dams up to and including concentrations of 5,000 ppm. Methanol exposure did not result in effects on maternal weight, since maternal weight gain of the methanol-exposed groups was similar to that of the sham-exposed control throughout pregnancy. Evaluation of the pups revealed a dose-related increase of foetuses per litter with extra cervical ribs which was statistically significant at 2,000 ppm and the higher concentrations. Dose-related increases in the incidences of cleft palate and of exencephaly were also observed, which were statistically significant at 5,000 ppm and the higher concentrations. Post implantation mortality was dose-related increased at concentrations of 7,500 ppm and above. Fetal body weight was not affected below 10,000 ppm. This value can be converted to the respective NOAECs of methyl acetate of about 3,000 mg methyl acetate/m3 (3 mg/L air) for developmental toxicity and ca. 15,000 mg/m3 (15 mg/L air) for maternal toxicity.

 

Conclusion on developmental toxicity/teratogenicity

There are no data on developmental toxicity of methyl acetate. However, due to the rapid hydrolysis of this compound it is justified to base hazard assessment with respect to reproduction on the toxicological properties of the immediate metabolites. Concerning the metabolites of methyl acetate, acetic acid appears to be of less significance, since there are no indications of a fetotoxic or teratogenic potential, whereas for methanol some embryo-/fetotoxic and teratogenic effects were demonstrated in rodents, however at relatively high concentrations, respectively maternal toxic concentrations only. A NOAEC/developmental toxicity for methanol of 1,000 ppm (1,300 mg methanol/m3) was derived from the inhalation study by NEDO (1987) in rats. The study with mice (Rogers et al., 1993) led to the same conclusion.

For acetic acid the data base is limited but does not indicate a potential for developmental toxicity. The data available for tert-butyl acetate form a prenatal developmental study with no teratological effecs supports this conclusion.

 

Literature

NEDO (1987). Toxicological Research of methanol as a fuel for Power Station, Summary Report on Tests with Monkeys, Rats and Mice. New Energy Development Organization. Tokyo, Japan.

NTIS (1977). No. PB-274670, FDA/BF-78/16. In: Life Sci. Res. Office, Fed. Am. Soc. Exp. Biol., Bethesda, MD.

Nelson BK, Brightwell WS, MacKenzie DR, Khan A, Burg JR, Weigel WW, Goad PT (1985). Teratological assessment of methanol and ethanol at high inhalation levels in rats. Fundam. App. Toxicol. 5, 727-736.

Nelson BK, Brightwell WS, Krieg Jr. EF (1990). Developmental toxicology of industrial alcohols: A summary of 13 alcohols administered by inhalation to rats. Toxicol. Ind. Health 6, 373-387.

Rogers JM, Mole ML, Chernoff N, Barbee BD, Turner C, Logson TR, Kavlock RJ (1993). The developmental toxicity of inhaled methanol in the CD-1 mouse, with quantitative dose-response modeling for estimation of benchmark doses. Teratology 47, 175-188.

Groth G. and Freundt KJ., (1994). Inhaled tert-Butyl Acetate and its Metabolite tert-Butyl Alcohol Accumulate in the Blood during Exposure. Hum Exp Toxicol.; 13(7): 478-480.

Lee EW, Terzo TS, D`Arcy JB, Gross KB, Schreck RM (1992). Lack of blood formate accumulation in humans following exposure to methanol vapor at the current permissible exposure limit.of 200 ppm. Am. Ind. Hyg. Assoc. J. 53, 99-104.

MAK Collection for Occupational Health and Safety (2016), Vol 1, No 2: tert-Butyl acetate p. 578-596

Perkins RA, Ward KW, Pollack GM (1995). A Pharmacokinetic model of inhaled methanol in humans and comparison to methanol disposition in mice and rats. Environmental Health Perspectives 103, 726-733.

Yang Y.S., Ahn T.H., Lee J.C., Moon C.J., Kim S.H., Park S.C., Chung Y.H., Kim H.Y. and Kim J.C. (2007): Effects of Tert–Butyl Acetate on Maternal Toxicity and Embryo-Fetal Development in Sprague-Dawley Rats. Birth Defects Research (Part B) 80: 374–382.

EFSA (European Food Safety Authority) (2012): SCIENTIFIC OPINION Scientific Opinion on the evaluation of the substances currently on the list in the annex to Commission Directive 96/3/EC as acceptable previous cargoes for edible fats and oils – Part II of III. EFSA Journal 2012; 10 85): 2703

Yang et al. (2007): Effects of tert-butyl acetate on maternal toxicity and embryo-fetal development in Spargue-Dawley rats. Birth Defects Research (Part B) 80: 374 - 382.

Justification for classification or non-classification

Based on the data for the hydrolysis products methyl acetate dose not fulfill the criteria for classification as toxic to fertility or developmental toxicity according to Regulation (EC) No 1272/2008. Methanol developmental toxicity is not seen as relevant for classification as discussed in the RAC opinion on methanol classification from 2014.